title: Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis.
abstract: The objective of this study was to determine the effect of systemic delivery of prednisolone phosphate (PLP) encapsulated within long circulating 'stealth' liposomes on bone erosion and osteoclast activity during experimental antigen-induced arthritis (AIA). Liposomal PLP strongly suppressed knee joint swelling, synovial infiltrate and bone erosion in antigen-induced arthritis. The number of active osteoclasts was not only suppressed in bone lesions near inflamed synovium, but also within the trabecular bone of the tibia, suggesting a systemic suppression of osteoclast activation. Furthermore, liposomal PLP directly blocked osteoclast differentiation and bone resorption in vitro while it also suppressed expression of osteoclast differentiation factors M-CSF and RANKL in the synovium. Targeting studies showed that liposomes are most efficiently phagocytosed by macrophages and early precursors of osteoclasts in the bone marrow rather than by mature osteoclasts, indicating a possible inhibition of osteoclast differentiation from an early stage.
  
  
  CONCLUSIONS
  Liposomal glucocorticoid delivery rather than free PLP offers a more efficacious way to inhibit both inflammation and bone erosion in rheumatoid arthritis.
authors.affiliation: Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Hofkens
authors.forename: Lilyanne C
authors.initials: LC
authors.lastname: Grevers
authors.forename: Birgitte
authors.initials: B
authors.lastname: Walgreen
authors.forename: Teun J
authors.initials: TJ
authors.lastname: de Vries
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.forename: Peter L
authors.initials: PL
authors.lastname: van Lent
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000135:Acid Phosphatase / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056657:Cathepsin K / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D007527:Isoenzymes / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008081:Liposomes; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D055017:Monocyte-Macrophage Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011239:Prednisolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D053245:RANK Ligand / Q000235:genetics / Q000494:pharmacology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase; D014611:Vaccination
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D007527:Isoenzymes; D008081:Liposomes; D010714:Phosphatidylethanolamines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C029180:methylated bovine serum albumin; D015060:1,2-Dipalmitoylphosphatidylcholine; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C009022:prednisolone phosphate; D016173:Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D011239:Prednisolone; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse